Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases

BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies. Enrolled patients included seven patients with relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors described in this case series. MATERIALS AND METHODS: Forty patients with relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or testicular tumors were screened for CD30 expression; 14 patients had tumors that expressed CD30. Seven patients with CD30-expressing testicular cancer were enrolled in the treatment study: five patients with germ cell tumors, one patient with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every 3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles thereafter while the patient was receiving treatment. RESULTS: Two of seven patients achieved an objective response, including one durable complete response and one partial response at a single time point. Both responding patients had germ cell tumors. Treatment with brentuximab vedotin was generally well tolerated. CONCLUSION: Treatment of relapsed or refractory germ cell tumors with brentuximab vedotin can induce durable responses with a manageable toxicity profile. IMPLICATIONS FOR PRACTICE: This case series of seven patients with relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord stromal tumors demonstrates that brentuximab vedotin has activity against GCTs and is well tolerated in heavily pretreated patients with these aggressive tumor types. One patient achieved a complete response that has been durable for almost 4 years since the discontinuation of treatment with brentuximab vedotin. Therefore, brentuximab vedotin may be a valuable option for physicians who care for this difficult-to-treat patient population

Situating emotional experience

Psychological construction approaches to emotion suggest that emotional experience is situated and dynamic. Fear, for example, is typically studied in a physical danger context (e.g., threatening snake), but in the real world, it often occurs in social contexts, especially those involving social evaluation (e.g., public speaking). Understanding situated emotional experience is critical because adaptive responding is guided by situational context (e.g., inferring the intention of another in a social evaluation situation vs. monitoring the environment in a physical danger situation). In an fMRI study, we assessed situated emotional experience using a newly developed paradigm in which participants vividly imagine different scenarios from a first-person perspective, in this case scenarios involving either social evaluation or physical danger. We hypothesized that distributed neural patterns would underlie immersion in social evaluation and physical danger situations, with shared activity patterns across both situations in multiple sensory modalities and in circuitry involved in integrating salient sensory information, and with unique activity patterns for each situation type in coordinated large-scale networks that reflect situated responding. More specifically, we predicted that networks underlying the social inference and mentalizing involved in responding to a social threat (in regions that make up the “default mode” network) would be reliably more active during social evaluation situations. In contrast, networks underlying the visuospatial attention and action planning involved in responding to a physical threat would be reliably more active during physical danger situations. The results supported these hypotheses. In line with emerging psychological construction approaches, the findings suggest that coordinated brain networks offer a systematic way to interpret the distributed patterns that underlie the diverse situational contexts characterizing emotional life

Hazardous waste problem sites

Geology of the coastal lowlands, Boston to Kennebunk, Maine: The 76th annual meeting New England Intercollegiate Geological Conference, Danvers, Massachusetts, October 12-14, 1984: Trip A-

Primary interoceptive cortex activity during simulated experiences of the body

Studies of the classic exteroceptive sensory systems (e.g., vision, touch) consistently demonstrate that vividly imagining a sensory experience of the world – simulating it – is associated with increased activity in the corresponding primary sensory cortex. We hypothesized, analogously, that simulating internal bodily sensations would be associated with increased neural activity in primary interoceptive cortex. An immersive, language-based mental imagery paradigm was used to test this hypothesis (e.g., imagine your heart pounding during a roller coaster ride, your face drenched in sweat during a workout). During two neuroimaging experiments, participants listened to vividly described situations and imagined “being there” in each scenario. In Study 1, we observed significantly heightened activity in primary interoceptive cortex (of dorsal posterior insula) during imagined experiences involving vivid internal sensations. This effect was specific to interoceptive simulation: it was not observed during a separate affect focus condition in Study 1, nor during an independent Study 2 that did not involve detailed simulation of internal sensations (instead involving simulation of other sensory experiences). These findings underscore the large-scale predictive architecture of the brain and reveal that words can be powerful drivers of bodily experiences

Testing the Unitarity of the CKM Matrix with a Space-Based Neutron Decay Experiment

If the Standard Model is correct, and fundamental fermions exist only in the three generations, then the CKM matrix should be unitary. However, there remains a question over a deviation from unitarity from the value of the neutron lifetime. We discuss a simple space-based experiment that, at an orbit height of 500 km above Earth, would measure the kinetic-energy, solid-angle, flux spectrum of gravitationally bound neutrons (kinetic energy K<0.606 eV at this altitude). The difference between the energy spectrum of neutrons that come up from the Earth's atmosphere and that of the undecayed neutrons that return back down to the Earth would yield a measurement of the neutron lifetime. This measurement would be free of the systematics of laboratory experiments. A package of mass $<25$ kg could provide a 10^{-3} precision in two years.Comment: 10 pages, 4 figures. Revised and updated for publicatio

Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families.

IntroductionThe impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov ).MethodsIn both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2-15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2-17 years). Established QoL score severity bands provided clinical context.ResultsGreater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: - 4.6 vs. - 3.0; P &lt; 0.001; DLQI: - 5.2 vs. - 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: - 3.7 vs. - 2.7; P = 0.003).ConclusionCrisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial registrationAD-301: http://www.clinicaltrials.gov , NCT02118766; AD-302: http://www.clinicaltrials.gov , NCT02118792.FundingAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY

Model for Cameron band emission in comets: A case for EPOXI mission target comet 103P/Hartley 2

The CO2 production rate has been derived in comets using the Cameron band (a3Pi - X1Sigma) emission of CO molecule assuming that photodissociative excitation of CO2 is the main production mechanism of CO in a3Pi metastable state. We have devoloped a model for the production and loss of CO(a3Pi) which has been applied to comet 103P/Hartley 2: the target of EPOXI mission. Our model calculations show that photoelectron impact excitation of CO and dissociative excitation of CO2 can together contribute about 60-90% to the Cameron band emission. The modeled brightness of (0-0) Cameron band emission on comet Hartley 2 is consistent with Hubble Space Telescope observations for 3-5% CO2 (depending on model input solar flux) and 0.5% CO relative to water, where photoelectron impact contribution is about 50-75%. We suggest that estimation of CO2 abundances on comets using Cameron band emission may be reconsidered. We predict the height integrated column brightness of Cameron band of ~1300 R during EPOXI mission encounter period.Comment: 3 figure

Learning situated emotions

From the perspective of constructivist theories, emotion results from learning assemblies of relevant perceptual, cognitive, interoceptive, and motor processes in specific situations. Across emotional experiences over time, learned assemblies of processes accumulate in memory that later underlie emotional experiences in similar situations. A neuroimaging experiment guided participants to experience (and thus learn) situated forms of emotion, and then assessed whether participants tended to experience situated forms of the emotion later. During the initial learning phase, some participants immersed themselves in vividly imagined fear and anger experiences involving physical harm, whereas other participants immersed themselves in vividly imagined fear and anger experiences involving negative social evaluation. In the subsequent testing phase, both learning groups experienced fear and anger while their neural activity was assessed with functional magnetic resonance imaging (fMRI). A variety of results indicated that the physical and social learning groups incidentally learned different situated forms of a given emotion. Consistent with constructivist theories, these findings suggest that learning plays a central role in emotion, with emotion adapted to the situations in which it is experienced